The 1,2,4-triazole moiety is an important and versatile pharmacophore often found as a structural unit in diverse pharmaceutical classes. Antifungal imidazoles and indeed almost any important pharmaceutical, in which a five-membered nitrogen heterocyclic residue is incorporated, can be synthesized with a 1,2,4-triazole as a surrogate for that imidazole with retention of the model compound's original pharmacologic activity (Angibaud et al. Bioorg. Med. Chem. Lett. 2003 13:4361–4364). Biological pathways requiring histidine can be manipulated into accepting and incorporating the triazole analogue into the resulting protein (Ikeda et al. Protein Eng. 2003 16:699–706). Furthermore, the 1,2,4-triazole has been observed as a bioisostere for a phenyl ring in the PPARα agonists being explored as lipid-lowering drugs (Xu et al. J. Med. Chem. 2003 46:5121–5124).
A functionalized 1,2,4-triazole attached to a benzonitrile moiety is in clinical trials for breast cancer and is showing significant activity (Tominaga, T. and Suzuki, T. Anticancer Res. 2003 4:3533–3542). 1,2,4-Triazoles with alkylamino side chains were inhibitory against a host of malignant cell lines (Demirbas et al. Bioorg. Med. Chem. 2002 10:3717–3723). Dimers of 1,2,4-triazol-5-thiols were active against seven cancer types (Holla et al. Eur. J. Med. Chem. 2002 37:511–517). Both antitumor and anti-HIV activity were observed in triazoles fused to benzene sulfonamides (Pomarnacka E, Kozlarska-Kedra I, Farmaco 2003 58:423–429).
Fused ring systems in which the 1,2,4-triazole nucleus is the core of a larger heterocyclic pharmaceutical are showing considerable therapeutic promise. Catarzi reported that a triazole-quinoxaline class was potentially useful in neuroprotection (treatment and prevention of acute and chronic neurological disorders) (Catarzi et al. J. Med. Chem. 2004 47:262–272). Tourirte found modest inhibition of the replication of HIV by triazole-pyrimidines (Tourirte et al. Nucleosides Nucleotide Nucleic Acids. 2003 22:1985–1993).
Thus, the triazole nucleus is used widely in drug design and development.